Table of Contents
International Journal of Molecular Imaging
Volume 2011 (2011), Article ID 709416, 7 pages
http://dx.doi.org/10.1155/2011/709416
Research Article

Synthesis and In Vitro Evaluation of Novel Nortropane Derivatives as Potential Radiotracers for Muscarinic M2 Receptors

1Department of Nuclear Medicine, Medical Center Alkmaar, Wilhelminalaan 12, 1815 JD Alkmaar, The Netherlands
2Department of Organic Chemistry, Eindhoven University of Technology, Den Dolech 2, 5600 MB Eindhoven, The Netherlands
3GE Healthcare, Cygne Center, De Rondom 8, 5612 AP Eindhoven, The Netherlands
4Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

Received 24 November 2010; Revised 3 March 2011; Accepted 25 March 2011

Academic Editor: Guy Bormans

Copyright © 2011 Remco J. J. Knol et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Disturbances of the cerebral cholinergic neurotransmitter system are present in neurodegenerative disorders. SPECT or PET imaging, using radiotracers that selectively target muscarinic receptor subtypes, may be of value for in vivo evaluation of such conditions. 6β-acetoxynortropane, a potent muscarinic M2 receptor agonist, has previously demonstrated nanomolar affinity and high selectivity for this receptor. Based on this compound we synthesized four nortropane derivatives that are potentially suitable for SPECT imaging of the M2 receptor. 6β-acetoxynortropane and the novel derivatives were tested in vitro for affinity to the muscarinic M1−3 receptors. The original 6β-acetoxynortropane displayed high affinity (  nM) to M2 receptors and showed good selectivity ratios to the M1 (65-fold ratio) and the M3 (70-fold ratio) receptors. All new derivatives showed reduced affinity to the M2 subtype and loss of subtype selectivity. It is therefore concluded that the newly synthesized derivatives are not suitable for human SPECT imaging of M2 receptors.